Stimulation by 1alpha,25(OH)2-vitamin D3 of whole cell chloride currents in osteoblastic ROS 17/2.8 cells. A structure-function study.

The Journal of Biological Chemistry
Laura P Zanello, A W Norman

Abstract

1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3) can generate biological responses via genomic and nongenomic mechanisms. This article reports for the first time the effects of 1alpha,25(OH)2D3 and structurally related analogs on whole cell chloride currents in osteoblastic cells. 1alpha,25(OH)2D3 promoted the rapid enhancement of outwardly rectifying Cl- currents in 93% of the osteoblasts in a concentration-dependent manner, with a maximal increase of about 4-fold between 0.5 and 5 nM. This effect of 1alpha,25(OH)2D3 was blocked by 1 nM stereoisomer 1beta,25(OH)2D3 when added to the bath before 1alpha,25(OH)2D3. On the other hand, 1 nM of the 6-s-cis locked analog 1alpha,25(OH)2-lumisterol3 significantly increased by about 2.2-fold outward Cl- currents in the ROS 17/2.8 cells, whereas the increase promoted by same concentration of the 6-s-trans locked analog 1alpha,25(OH)2-tachysterol (0.8-fold) was significantly lower, suggesting that the 6-s-cis locked or steroid-like form was preferred over the extended 6-s-trans conformer to promote these rapid effects of the hormone. We conclude that the agonist effects of 1alpha,25(OH)2D3 in osteoblasts at the cellular membrane level seem to be determined by some structural features of t...Continue Reading

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Citations

Apr 7, 2005·Molecular Aspects of Medicine·Manuel Montero-Odasso, Gustavo Duque
Nov 5, 2002·Biochemical and Biophysical Research Communications·Anthony W NormanJune E Bishop
Feb 17, 2001·Steroids·A W Norman
Nov 15, 2002·Molecular and Cellular Endocrinology·Anthony W NormanHelen L Henry
Apr 1, 2010·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Katie M DixonRebecca S Mason
Aug 25, 2004·Proceedings of the National Academy of Sciences of the United States of America·Mathew T MizwickiAnthony W Norman
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Aug 10, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·D Lovitch, M L Christianson
Jun 25, 2013·Pharmacology & Therapeutics·Audrey H PoonQutayba Hamid
Feb 6, 2004·Proceedings of the National Academy of Sciences of the United States of America·Laura P Zanello, Anthony W Norman
Jan 9, 2007·The Journal of Steroid Biochemistry and Molecular Biology·Zhang XiaoyuLaura P Zanello
Aug 30, 2011·Best Practice & Research. Clinical Endocrinology & Metabolism·Mark R HausslerAnthony W Norman
Feb 7, 2006·Steroids·Laura P Zanello, Anthony Norman
Mar 3, 2004·Journal of Cellular Biochemistry·Mathew T MizwickiAnthony W Norman
Apr 16, 2008·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Xiaoyu Zhang, Laura P Zanello
Aug 10, 2010·Acta Crystallographica. Section D, Biological Crystallography·Shinji KakudaMidori Takimoto-Kamimura
Jan 7, 2004·Nature Reviews. Drug Discovery·Anthony W NormanDerek P G Norman
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Oct 29, 1998·The Journal of Biological Chemistry·J B SafranM C Farach-Carson

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